This competing renewal application responds to program announcement PA-95-056, Biobehavioral Pain Research (NIH Guide, 24(15)1995). Its key themes are measurement of pain, psychophysiological indicators, the affective dimension of pain, and elucidation of individual differences. Because this work relates to the acute pain associated with invasive procedures in the cancer setting and dentistry, this application fits the missions of the NCI and NIDCR. This proposal addresses the affective component of pain in human subjects, offering a theoretical basis for defining and quantifying it. The sensory awareness of a transient injurious event takes place against a background of co-existing central nervous system and autonomically mediated responses that closely resemble Sokolov's defense response (DR). Combining psychophysiology with structural equation modeling, the applicants have defined the DR as a multivariate construct. The aims of this 5 year application are to: 1) determine whether the DR associated with noxious stimulation is a subcortical protective reflex or a complex, cortically mediated response that depends upon attentional processes; 2) determine whether central noradrenergic circuits play an essential role in the DR; 3) determine whether the pre-existing affective context in which a painful stimulus occurs enhances or diminishes psychophysiological and subjective responses to that stimulus; and 4) quantify, evaluate and further clarify individual differences, including sex effects, in the DR. The applicants propose three studies. The first (n=180) will test the hypothesis that distraction from a noxious event can alter the DR. The second (n=180) evaluates the hypothesis that pharmacological manipulation of noradrenergically-mediated central arousal with clonidine and yohimbine impairs or enhances the DR, respectively. The third (n=100) tests the hypotheses that subjects~ psychophysiological and rating responses to a noxious stimulus vary on the basis of affective context; positive valence will attenuate and negative valence will amplify the responses. This work will advance current understanding of the affective mechanisms of pain by introducing and evaluating new theory, contributing a new approach to the measurement of pain, and demonstrating the value of structural equation modeling for human laboratory research.